Fragment-Based Drug Discovery

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<StructureSection load='1ysi' size='500' side='right' caption='Structure of Bcl-xl/Acyl-sulfonamide complex (PDB entry [[1ysi]])' scene=''>
<StructureSection load='1ysi' size='500' side='right' caption='Structure of Bcl-xl/Acyl-sulfonamide complex (PDB entry [[1ysi]])' scene=''>
=== Apoptosis and Cancer ===
=== Apoptosis and Cancer ===
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Apoptosis, or programmed cell death, is a natural mechanism in which a damaged cell dies in order to prevent further damage to the multicellular organism. The absence of apoptosis in damaged cells can lead to many types of cancers and other diseases. In certain types of cancers, a family of proteins, known as the Bcl-2 family, has been observed as being over-expressed compared to normal, healthy cells.<ref>Oltersdorf T., Elmore S.W., Shoemaker A.R. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Vol 435|2 June 2005|doi:10.1038/nature03579</ref>
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Apoptosis, or programmed cell death, is a natural mechanism in which a damaged cell dies in order to prevent further damage to the multicellular organism. The absence of apoptosis in damaged cells can lead to many types of cancers and other diseases. In certain types of cancers, a family of proteins, known as the Bcl-2 family, has been observed as being over-expressed compared to normal, healthy cells.<ref>Oltersdorf T., Elmore S.W., Shoemaker A.R. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Vol 435|2 June 2005|doi:10.1038/nature03579</ref> There is also evidence to suggest that Bcl-2 over-expression may also contribute to chemo-resistance.
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Bcl-xl is a specific protein of the Bcl-2 family that, when over-expressed, may act as an initiator of tumor formation. There is also evidence to suggest that Bcl-xl expression may also contribute to chemo-resistance. The protein includes seven <scene name='Sandbox_reserved_394/Alpha_helices/1'>alpha helices</scene> and no beta sheets.
 
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=== Bcl-xl: a member of the Bcl-2 family ===
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Bcl-xl is a member of the Bcl-2 family. The protein includes seven <scene name='Sandbox_reserved_394/Alpha_helices/1'>alpha helices</scene> and no beta sheets.
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Inhibition of the over-expression of the Bcl-2 family of proteins has been shown to be effective at inducing tumor regression and increasing chemo-sensitivity. This represents the binding of an <scene name='Sandbox_reserved_394/Paclitaxel/1'>acyl-sulfonamide</scene> to the anti-apoptotic protein, <scene name='Sandbox_reserved_394/Bcl-xl/1'>Bcl-xl</scene>.
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Inhibition of the over-expression of this protein has been shown to be effective at inducing tumor regression and increasing chemo-sensitivity. This represents the binding of an <scene name='Sandbox_reserved_394/Paclitaxel/1'>acyl-sulfonamide</scene> to the anti-apoptotic protein, <scene name='Sandbox_reserved_394/Bcl-xl/1'>Bcl-xl</scene>.

Revision as of 00:59, 3 October 2012

Apoptosis by Inhibition of Bcl-2 Family Proteins

Structure of Bcl-xl/Acyl-sulfonamide complex (PDB entry 1ysi)

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References

  1. Oltersdorf T., Elmore S.W., Shoemaker A.R. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Vol 435|2 June 2005|doi:10.1038/nature03579

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Justin Weekley, Arthur Cox, Jaime Prilusky

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